Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study
Identifieur interne : 001122 ( Ncbi/Curation ); précédent : 001121; suivant : 001123Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study
Auteurs : Frances M K. Williams [Royaume-Uni] ; Angela M. Carter [Royaume-Uni] ; Pirro G. Hysi [Royaume-Uni] ; Gabriela Surdulescu [Royaume-Uni] ; Dylan Hodgkiss [Royaume-Uni] ; Nicole Soranzo [Royaume-Uni, États-Unis, Finlande] ; Matthew Traylor [Royaume-Uni] ; Steve Bevan [Royaume-Uni] ; Martin Dichgans [Allemagne] ; Peter M W. Rothwell [Royaume-Uni] ; Cathie Sudlow [Royaume-Uni] ; Martin Farrall [Royaume-Uni] ; Kaisa Silander [Finlande] ; Mari Kaunisto [Finlande] ; Peter Wagner [Finlande] ; Olli Saarela [Finlande] ; Kari Kuulasmaa [Finlande] ; Jarmo Virtamo [Finlande] ; Veikko Salomaa [Finlande] ; Philippe Amouyel [France] ; Dominique Arveiler [France] ; Jean Ferrieres [France] ; Per-Gunnar Wiklund [Suède] ; M. Arfan Ikram [Pays-Bas] ; Albert Hofman [Pays-Bas] ; Giorgio B. Boncoraglio [Italie] ; Eugenio A. Parati [Italie] ; Anna Helgadottir [Royaume-Uni, Islande] ; Solveig Gretarsdottir [Islande] ; Unnur Thorsteinsdottir [Islande] ; Gudmar Thorleifsson [Islande] ; Kari Stefansson [Islande] ; Sudha Seshadri [États-Unis] ; Anita Destefano [États-Unis] ; Andreas Gschwendtner [Allemagne] ; Bruce Psaty [États-Unis] ; Will Longstreth [États-Unis] ; Braxton D. Mitchell [Royaume-Uni] ; Yu-Ching Cheng [Royaume-Uni] ; Robert Clarke [Italie] ; Marco Ferrario [États-Unis] ; Joshua C. Bis [Australie] ; Christopher Levi [Australie, États-Unis] ; John Attia [Australie, États-Unis] ; Elizabeth G. Holliday [Australie, États-Unis] ; Rodney J. Scott [Australie, États-Unis] ; Myriam Fornage [Royaume-Uni] ; Pankaj Sharma [États-Unis] ; Karen L. Furie [États-Unis] ; Jonathan Rosand [États-Unis] ; Mike Nalls [États-Unis] ; James Meschia [États-Unis] ; Thomas H. Mosely [Royaume-Uni] ; Alun Evans ; Aarno Palotie [Royaume-Uni, États-Unis, Finlande] ; Hugh S. Markus [Royaume-Uni] ; Peter J. Grant [Royaume-Uni] ; Tim D. Spector [Royaume-Uni]Source :
- Annals of Neurology [ 0364-5134 ] ; 2013.
Abstract
End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.
Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3).
Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (
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DOI: 10.1002/ana.23838
PubMed: 23381943
PubMed Central: 3582024
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xml:lang="fr">France</country><wicri:regionArea>Lille</wicri:regionArea></affiliation></author><author><name sortKey="Arveiler, Dominique" sort="Arveiler, Dominique" uniqKey="Arveiler D" first="Dominique" last="Arveiler">Dominique Arveiler</name><affiliation wicri:level="1"><nlm:aff id="au14"><institution>Department of Epidemiology and Public Health, University of Strasbourg</institution><addr-line>Strasbourg, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Strasbourg</wicri:regionArea></affiliation></author><author><name sortKey="Ferrieres, Jean" sort="Ferrieres, Jean" uniqKey="Ferrieres J" first="Jean" last="Ferrieres">Jean Ferrieres</name><affiliation wicri:level="3"><nlm:aff id="au15"><institution>Department of Epidemiology, Faculty of Medicine</institution><addr-line>Toulouse-Purpan, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Toulouse-Purpan, Toulouse</wicri:regionArea><placeName><region 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Arfan Ikram</name><affiliation wicri:level="1"><nlm:aff id="au17"><institution>Department of Epidemiology, Erasmus University Medical Center</institution><addr-line>Rotterdam, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation wicri:level="1"><nlm:aff id="au17"><institution>Department of Epidemiology, Erasmus University Medical Center</institution><addr-line>Rotterdam, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Boncoraglio, Giorgio B" sort="Boncoraglio, Giorgio B" uniqKey="Boncoraglio G" first="Giorgio B" last="Boncoraglio">Giorgio B. Boncoraglio</name><affiliation wicri:level="1"><nlm:aff id="au18"><institution>Department of Neurology, Research Hospital of the Neurological Institute “Carlo Besta,”</institution><addr-line>Milan, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Milan</wicri:regionArea></affiliation></author><author><name sortKey="Parati, Eugenio A" sort="Parati, Eugenio A" uniqKey="Parati E" first="Eugenio A" last="Parati">Eugenio A. Parati</name><affiliation wicri:level="1"><nlm:aff id="au18"><institution>Department of Neurology, Research Hospital of the Neurological Institute “Carlo Besta,”</institution><addr-line>Milan, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Milan</wicri:regionArea></affiliation></author><author><name sortKey="Helgadottir, Anna" sort="Helgadottir, Anna" uniqKey="Helgadottir A" first="Anna" last="Helgadottir">Anna Helgadottir</name><affiliation wicri:level="1"><nlm:aff id="au10"><institution>Wellcome Trust Centre for Human Genetics and Department of Cardiovascular Medicine, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Gretarsdottir, Solveig" sort="Gretarsdottir, Solveig" uniqKey="Gretarsdottir S" first="Solveig" last="Gretarsdottir">Solveig Gretarsdottir</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name><affiliation wicri:level="2"><nlm:aff id="au20"><institution>Boston University Schools of Medicine and Public Health</institution><addr-line>Boston, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au21"><institution>Framingham Heart Study</institution><addr-line>Framingham, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Framingham</wicri:cityArea></affiliation><affiliation><nlm:aff id="au22"><institution>Departments of Health Services, University of Washington</institution><addr-line>Seattlem WA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Destefano, Anita" sort="Destefano, Anita" uniqKey="Destefano A" first="Anita" last="Destefano">Anita Destefano</name><affiliation wicri:level="2"><nlm:aff id="au20"><institution>Boston University Schools of Medicine and Public Health</institution><addr-line>Boston, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au21"><institution>Framingham Heart Study</institution><addr-line>Framingham, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Framingham</wicri:cityArea></affiliation><affiliation><nlm:aff id="au22"><institution>Departments of Health Services, University of Washington</institution><addr-line>Seattlem WA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gschwendtner, Andreas" sort="Gschwendtner, Andreas" uniqKey="Gschwendtner A" first="Andreas" last="Gschwendtner">Andreas Gschwendtner</name><affiliation wicri:level="1"><nlm:aff id="au7"><institution>Institute for Stroke and Dementia Research, Klinikum der Universität Munich, Ludwig-Maximilians-University</institution><addr-line>Munich, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Munich</wicri:regionArea></affiliation></author><author><name sortKey="Psaty, Bruce" sort="Psaty, Bruce" uniqKey="Psaty B" first="Bruce" last="Psaty">Bruce Psaty</name><affiliation wicri:level="2"><nlm:aff id="au23"><institution>Epidemiology, Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au24"><institution>Medicine, and Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au25"><institution>Group Health Research Institute, Group Health</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation><nlm:aff id="au26"><institution>Department of Neurology, University of Washington</institution><addr-line>WA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Longstreth, Will" sort="Longstreth, Will" uniqKey="Longstreth W" first="Will" last="Longstreth">Will Longstreth</name><affiliation wicri:level="2"><nlm:aff id="au23"><institution>Epidemiology, Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au24"><institution>Medicine, and Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au27"><institution>Department of Medicine, University of Maryland</institution><addr-line>Baltimore, MD</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D" last="Mitchell">Braxton D. Mitchell</name><affiliation wicri:level="1"><nlm:aff id="au28"><institution>Clinical Trial Service Unit, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Yu Ching" sort="Cheng, Yu Ching" uniqKey="Cheng Y" first="Yu-Ching" last="Cheng">Yu-Ching Cheng</name><affiliation wicri:level="1"><nlm:aff id="au28"><institution>Clinical Trial Service Unit, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Robert" sort="Clarke, Robert" uniqKey="Clarke R" first="Robert" last="Clarke">Robert Clarke</name><affiliation wicri:level="1"><nlm:aff id="au29"><institution>University of Insubria</institution><addr-line>Varese, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Varese</wicri:regionArea></affiliation></author><author><name sortKey="Ferrario, Marco" sort="Ferrario, Marco" uniqKey="Ferrario M" first="Marco" last="Ferrario">Marco Ferrario</name><affiliation wicri:level="2"><nlm:aff id="au30"><institution>Cardiovascular Health Research Unit, Department of Medicine, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C" last="Bis">Joshua C. Bis</name><affiliation wicri:level="1"><nlm:aff id="au31"><institution>University of Newcastle</institution><addr-line>Callaghan, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Callaghan</wicri:regionArea></affiliation></author><author><name sortKey="Levi, Christopher" sort="Levi, Christopher" uniqKey="Levi C" first="Christopher" last="Levi">Christopher Levi</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Attia, John" sort="Attia, John" uniqKey="Attia J" first="John" last="Attia">John Attia</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G" last="Holliday">Elizabeth G. Holliday</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J" last="Scott">Rodney J. Scott</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation wicri:level="1"><nlm:aff id="au35"><institution>Imperial College Cerebrovascular Research Unit, Imperial College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Sharma, Pankaj" sort="Sharma, Pankaj" uniqKey="Sharma P" first="Pankaj" last="Sharma">Pankaj Sharma</name><affiliation wicri:level="2"><nlm:aff id="au36"><institution>Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School</institution><addr-line>Boston, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Furie, Karen L" sort="Furie, Karen L" uniqKey="Furie K" first="Karen L" last="Furie">Karen L. Furie</name><affiliation wicri:level="2"><nlm:aff id="au37"><institution>Department of Neurology, Mayo Clinic</institution><addr-line>Jacksonville, FL, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jacksonville, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Rosand, Jonathan" sort="Rosand, Jonathan" uniqKey="Rosand J" first="Jonathan" last="Rosand">Jonathan Rosand</name><affiliation wicri:level="2"><nlm:aff id="au37"><institution>Department of Neurology, Mayo Clinic</institution><addr-line>Jacksonville, FL, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jacksonville, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Nalls, Mike" sort="Nalls, Mike" uniqKey="Nalls M" first="Mike" last="Nalls">Mike Nalls</name><affiliation wicri:level="2"><nlm:aff id="au38"><institution>University of Mississippi Medical Center</institution><addr-line>Jackson, MS</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État du Mississippi</region></placeName><wicri:cityArea>Jackson</wicri:cityArea></affiliation></author><author><name sortKey="Meschia, James" sort="Meschia, James" uniqKey="Meschia J" first="James" last="Meschia">James Meschia</name><affiliation wicri:level="2"><nlm:aff id="au38"><institution>University of Mississippi Medical Center</institution><addr-line>Jackson, MS</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État du Mississippi</region></placeName><wicri:cityArea>Jackson</wicri:cityArea></affiliation></author><author><name sortKey="Mosely, Thomas H" sort="Mosely, Thomas H" uniqKey="Mosely T" first="Thomas H" last="Mosely">Thomas H. Mosely</name><affiliation wicri:level="1"><nlm:aff id="au39"><institution>Queen's University of Belfast</institution><addr-line>Belfast, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Belfast</wicri:regionArea></affiliation></author><author><name sortKey="Evans, Alun" sort="Evans, Alun" uniqKey="Evans A" first="Alun" last="Evans">Alun Evans</name></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus</institution><addr-line>Hinxton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Hinxton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au4"><institution>Program in Medical and Population Genetics and Genetic Analysis Platform, Broad Institute of Massachusetts Institute of Technology and Harvard</institution><addr-line>Cambridge, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au5"><institution>Department of Medical Genetics, University of Helsinki and University Central Hospital</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au11"><institution>Institute for Molecular Medicine Finland, University of Helsinki</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Markus, Hugh S" sort="Markus, Hugh S" uniqKey="Markus H" first="Hugh S" last="Markus">Hugh S. Markus</name><affiliation wicri:level="1"><nlm:aff id="au6"><institution>Stroke and Dementia Research Centre, St George's University of London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Grant, Peter J" sort="Grant, Peter J" uniqKey="Grant P" first="Peter J" last="Grant">Peter J. Grant</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Division of Cardiovascular and Diabetes Research, University of Leeds</institution><addr-line>Leeds, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leeds</wicri:regionArea></affiliation></author><author><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D" last="Spector">Tim D. Spector</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Twin Research and Genetic Epidemiology, King's College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23381943</idno><idno type="pmc">3582024</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582024</idno><idno type="RBID">PMC:3582024</idno><idno type="doi">10.1002/ana.23838</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002239</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002239</idno><idno type="wicri:Area/Pmc/Curation">002089</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002089</idno><idno type="wicri:Area/Pmc/Checkpoint">001A38</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001A38</idno><idno type="wicri:Area/Ncbi/Merge">001122</idno><idno type="wicri:Area/Ncbi/Curation">001122</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ischemic Stroke Is Associated with the <italic>ABO</italic> Locus: The EuroCLOT Study</title><author><name sortKey="Williams, Frances M K" sort="Williams, Frances M K" uniqKey="Williams F" first="Frances M K" last="Williams">Frances M K. Williams</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Twin Research and Genetic Epidemiology, King's College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Carter, Angela M" sort="Carter, Angela M" uniqKey="Carter A" first="Angela M" last="Carter">Angela M. Carter</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Division of Cardiovascular and Diabetes Research, University of Leeds</institution><addr-line>Leeds, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leeds</wicri:regionArea></affiliation></author><author><name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G" last="Hysi">Pirro G. Hysi</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Twin Research and Genetic Epidemiology, King's College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Surdulescu, Gabriela" sort="Surdulescu, Gabriela" uniqKey="Surdulescu G" first="Gabriela" last="Surdulescu">Gabriela Surdulescu</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Twin Research and Genetic Epidemiology, King's College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Hodgkiss, Dylan" sort="Hodgkiss, Dylan" uniqKey="Hodgkiss D" first="Dylan" last="Hodgkiss">Dylan Hodgkiss</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Twin Research and Genetic Epidemiology, King's College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus</institution><addr-line>Hinxton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Hinxton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au4"><institution>Program in Medical and Population Genetics and Genetic Analysis Platform, Broad Institute of Massachusetts Institute of Technology and Harvard</institution><addr-line>Cambridge, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au5"><institution>Department of Medical Genetics, University of Helsinki and University Central Hospital</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Traylor, Matthew" sort="Traylor, Matthew" uniqKey="Traylor M" first="Matthew" last="Traylor">Matthew Traylor</name><affiliation wicri:level="1"><nlm:aff id="au6"><institution>Stroke and Dementia Research Centre, St George's University of London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Bevan, Steve" sort="Bevan, Steve" uniqKey="Bevan S" first="Steve" last="Bevan">Steve Bevan</name><affiliation wicri:level="1"><nlm:aff id="au6"><institution>Stroke and Dementia Research Centre, St George's University of London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Dichgans, Martin" sort="Dichgans, Martin" uniqKey="Dichgans M" first="Martin" last="Dichgans">Martin Dichgans</name><affiliation wicri:level="1"><nlm:aff id="au7"><institution>Institute for Stroke and Dementia Research, Klinikum der Universität Munich, Ludwig-Maximilians-University</institution><addr-line>Munich, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Munich</wicri:regionArea></affiliation></author><author><name sortKey="Rothwell, Peter M W" sort="Rothwell, Peter M W" uniqKey="Rothwell P" first="Peter M W" last="Rothwell">Peter M W. Rothwell</name><affiliation wicri:level="1"><nlm:aff id="au8"><institution>Stroke Prevention Research Unit, University Department of Clinical Neurology, Oxford University</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Sudlow, Cathie" sort="Sudlow, Cathie" uniqKey="Sudlow C" first="Cathie" last="Sudlow">Cathie Sudlow</name><affiliation wicri:level="1"><nlm:aff id="au9"><institution>Division of Clinical Neurosciences, University of Edinburgh</institution><addr-line>Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Farrall, Martin" sort="Farrall, Martin" uniqKey="Farrall M" first="Martin" last="Farrall">Martin Farrall</name><affiliation wicri:level="1"><nlm:aff id="au10"><institution>Wellcome Trust Centre for Human Genetics and Department of Cardiovascular Medicine, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Silander, Kaisa" sort="Silander, Kaisa" uniqKey="Silander K" first="Kaisa" last="Silander">Kaisa Silander</name><affiliation wicri:level="1"><nlm:aff id="au11"><institution>Institute for Molecular Medicine Finland, University of Helsinki</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Kaunisto, Mari" sort="Kaunisto, Mari" uniqKey="Kaunisto M" first="Mari" last="Kaunisto">Mari Kaunisto</name><affiliation wicri:level="1"><nlm:aff id="au11"><institution>Institute for Molecular Medicine Finland, University of Helsinki</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Wagner, Peter" sort="Wagner, Peter" uniqKey="Wagner P" first="Peter" last="Wagner">Peter Wagner</name><affiliation wicri:level="1"><nlm:aff id="au11"><institution>Institute for Molecular Medicine Finland, University of Helsinki</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Saarela, Olli" sort="Saarela, Olli" uniqKey="Saarela O" first="Olli" last="Saarela">Olli Saarela</name><affiliation wicri:level="1"><nlm:aff id="au12"><institution>Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Kuulasmaa, Kari" sort="Kuulasmaa, Kari" uniqKey="Kuulasmaa K" first="Kari" last="Kuulasmaa">Kari Kuulasmaa</name><affiliation wicri:level="1"><nlm:aff id="au12"><institution>Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Virtamo, Jarmo" sort="Virtamo, Jarmo" uniqKey="Virtamo J" first="Jarmo" last="Virtamo">Jarmo Virtamo</name><affiliation wicri:level="1"><nlm:aff id="au12"><institution>Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Salomaa, Veikko" sort="Salomaa, Veikko" uniqKey="Salomaa V" first="Veikko" last="Salomaa">Veikko Salomaa</name><affiliation wicri:level="1"><nlm:aff id="au12"><institution>Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation wicri:level="1"><nlm:aff id="au13"><institution>Department of Epidemiology and Public Health, Pasteur Institute of Lille</institution><addr-line>Lille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lille</wicri:regionArea></affiliation></author><author><name sortKey="Arveiler, Dominique" sort="Arveiler, Dominique" uniqKey="Arveiler D" first="Dominique" last="Arveiler">Dominique Arveiler</name><affiliation wicri:level="1"><nlm:aff id="au14"><institution>Department of Epidemiology and Public Health, University of Strasbourg</institution><addr-line>Strasbourg, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Strasbourg</wicri:regionArea></affiliation></author><author><name sortKey="Ferrieres, Jean" sort="Ferrieres, Jean" uniqKey="Ferrieres J" first="Jean" last="Ferrieres">Jean Ferrieres</name><affiliation wicri:level="3"><nlm:aff id="au15"><institution>Department of Epidemiology, Faculty of Medicine</institution><addr-line>Toulouse-Purpan, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Toulouse-Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Wiklund, Per Gunnar" sort="Wiklund, Per Gunnar" uniqKey="Wiklund P" first="Per-Gunnar" last="Wiklund">Per-Gunnar Wiklund</name><affiliation wicri:level="1"><nlm:aff id="au16"><institution>Department of Internal Medicine, University of Umeå</institution><addr-line>Umeå, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Umeå</wicri:regionArea></affiliation></author><author><name sortKey="Arfan Ikram, M" sort="Arfan Ikram, M" uniqKey="Arfan Ikram M" first="M" last="Arfan Ikram">M. Arfan Ikram</name><affiliation wicri:level="1"><nlm:aff id="au17"><institution>Department of Epidemiology, Erasmus University Medical Center</institution><addr-line>Rotterdam, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation wicri:level="1"><nlm:aff id="au17"><institution>Department of Epidemiology, Erasmus University Medical Center</institution><addr-line>Rotterdam, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Boncoraglio, Giorgio B" sort="Boncoraglio, Giorgio B" uniqKey="Boncoraglio G" first="Giorgio B" last="Boncoraglio">Giorgio B. Boncoraglio</name><affiliation wicri:level="1"><nlm:aff id="au18"><institution>Department of Neurology, Research Hospital of the Neurological Institute “Carlo Besta,”</institution><addr-line>Milan, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Milan</wicri:regionArea></affiliation></author><author><name sortKey="Parati, Eugenio A" sort="Parati, Eugenio A" uniqKey="Parati E" first="Eugenio A" last="Parati">Eugenio A. Parati</name><affiliation wicri:level="1"><nlm:aff id="au18"><institution>Department of Neurology, Research Hospital of the Neurological Institute “Carlo Besta,”</institution><addr-line>Milan, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Milan</wicri:regionArea></affiliation></author><author><name sortKey="Helgadottir, Anna" sort="Helgadottir, Anna" uniqKey="Helgadottir A" first="Anna" last="Helgadottir">Anna Helgadottir</name><affiliation wicri:level="1"><nlm:aff id="au10"><institution>Wellcome Trust Centre for Human Genetics and Department of Cardiovascular Medicine, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Gretarsdottir, Solveig" sort="Gretarsdottir, Solveig" uniqKey="Gretarsdottir S" first="Solveig" last="Gretarsdottir">Solveig Gretarsdottir</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation wicri:level="1"><nlm:aff id="au19"><institution>DeCODE Genetics</institution><addr-line>Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Reykjavik</wicri:regionArea></affiliation></author><author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name><affiliation wicri:level="2"><nlm:aff id="au20"><institution>Boston University Schools of Medicine and Public Health</institution><addr-line>Boston, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au21"><institution>Framingham Heart Study</institution><addr-line>Framingham, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Framingham</wicri:cityArea></affiliation><affiliation><nlm:aff id="au22"><institution>Departments of Health Services, University of Washington</institution><addr-line>Seattlem WA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Destefano, Anita" sort="Destefano, Anita" uniqKey="Destefano A" first="Anita" last="Destefano">Anita Destefano</name><affiliation wicri:level="2"><nlm:aff id="au20"><institution>Boston University Schools of Medicine and Public Health</institution><addr-line>Boston, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au21"><institution>Framingham Heart Study</institution><addr-line>Framingham, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Framingham</wicri:cityArea></affiliation><affiliation><nlm:aff id="au22"><institution>Departments of Health Services, University of Washington</institution><addr-line>Seattlem WA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gschwendtner, Andreas" sort="Gschwendtner, Andreas" uniqKey="Gschwendtner A" first="Andreas" last="Gschwendtner">Andreas Gschwendtner</name><affiliation wicri:level="1"><nlm:aff id="au7"><institution>Institute for Stroke and Dementia Research, Klinikum der Universität Munich, Ludwig-Maximilians-University</institution><addr-line>Munich, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Munich</wicri:regionArea></affiliation></author><author><name sortKey="Psaty, Bruce" sort="Psaty, Bruce" uniqKey="Psaty B" first="Bruce" last="Psaty">Bruce Psaty</name><affiliation wicri:level="2"><nlm:aff id="au23"><institution>Epidemiology, Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au24"><institution>Medicine, and Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au25"><institution>Group Health Research Institute, Group Health</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation><nlm:aff id="au26"><institution>Department of Neurology, University of Washington</institution><addr-line>WA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Longstreth, Will" sort="Longstreth, Will" uniqKey="Longstreth W" first="Will" last="Longstreth">Will Longstreth</name><affiliation wicri:level="2"><nlm:aff id="au23"><institution>Epidemiology, Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au24"><institution>Medicine, and Health Services, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au27"><institution>Department of Medicine, University of Maryland</institution><addr-line>Baltimore, MD</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D" last="Mitchell">Braxton D. Mitchell</name><affiliation wicri:level="1"><nlm:aff id="au28"><institution>Clinical Trial Service Unit, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Yu Ching" sort="Cheng, Yu Ching" uniqKey="Cheng Y" first="Yu-Ching" last="Cheng">Yu-Ching Cheng</name><affiliation wicri:level="1"><nlm:aff id="au28"><institution>Clinical Trial Service Unit, University of Oxford</institution><addr-line>Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Robert" sort="Clarke, Robert" uniqKey="Clarke R" first="Robert" last="Clarke">Robert Clarke</name><affiliation wicri:level="1"><nlm:aff id="au29"><institution>University of Insubria</institution><addr-line>Varese, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Varese</wicri:regionArea></affiliation></author><author><name sortKey="Ferrario, Marco" sort="Ferrario, Marco" uniqKey="Ferrario M" first="Marco" last="Ferrario">Marco Ferrario</name><affiliation wicri:level="2"><nlm:aff id="au30"><institution>Cardiovascular Health Research Unit, Department of Medicine, University of Washington</institution><addr-line>Seattle, WA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C" last="Bis">Joshua C. Bis</name><affiliation wicri:level="1"><nlm:aff id="au31"><institution>University of Newcastle</institution><addr-line>Callaghan, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Callaghan</wicri:regionArea></affiliation></author><author><name sortKey="Levi, Christopher" sort="Levi, Christopher" uniqKey="Levi C" first="Christopher" last="Levi">Christopher Levi</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Attia, John" sort="Attia, John" uniqKey="Attia J" first="John" last="Attia">John Attia</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G" last="Holliday">Elizabeth G. Holliday</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J" last="Scott">Rodney J. Scott</name><affiliation wicri:level="1"><nlm:aff id="au32"><institution>John Hunter Hospital</institution><addr-line>New Lambton Heights, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton Heights</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au33"><institution>Hunter Medical Research Institute</institution><addr-line>New Lambton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>New Lambton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au34"><institution>Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Sciences Center</institution><addr-line>Houston, TX</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation wicri:level="1"><nlm:aff id="au35"><institution>Imperial College Cerebrovascular Research Unit, Imperial College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Sharma, Pankaj" sort="Sharma, Pankaj" uniqKey="Sharma P" first="Pankaj" last="Sharma">Pankaj Sharma</name><affiliation wicri:level="2"><nlm:aff id="au36"><institution>Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School</institution><addr-line>Boston, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Furie, Karen L" sort="Furie, Karen L" uniqKey="Furie K" first="Karen L" last="Furie">Karen L. Furie</name><affiliation wicri:level="2"><nlm:aff id="au37"><institution>Department of Neurology, Mayo Clinic</institution><addr-line>Jacksonville, FL, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jacksonville, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Rosand, Jonathan" sort="Rosand, Jonathan" uniqKey="Rosand J" first="Jonathan" last="Rosand">Jonathan Rosand</name><affiliation wicri:level="2"><nlm:aff id="au37"><institution>Department of Neurology, Mayo Clinic</institution><addr-line>Jacksonville, FL, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jacksonville, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Nalls, Mike" sort="Nalls, Mike" uniqKey="Nalls M" first="Mike" last="Nalls">Mike Nalls</name><affiliation wicri:level="2"><nlm:aff id="au38"><institution>University of Mississippi Medical Center</institution><addr-line>Jackson, MS</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État du Mississippi</region></placeName><wicri:cityArea>Jackson</wicri:cityArea></affiliation></author><author><name sortKey="Meschia, James" sort="Meschia, James" uniqKey="Meschia J" first="James" last="Meschia">James Meschia</name><affiliation wicri:level="2"><nlm:aff id="au38"><institution>University of Mississippi Medical Center</institution><addr-line>Jackson, MS</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État du Mississippi</region></placeName><wicri:cityArea>Jackson</wicri:cityArea></affiliation></author><author><name sortKey="Mosely, Thomas H" sort="Mosely, Thomas H" uniqKey="Mosely T" first="Thomas H" last="Mosely">Thomas H. Mosely</name><affiliation wicri:level="1"><nlm:aff id="au39"><institution>Queen's University of Belfast</institution><addr-line>Belfast, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Belfast</wicri:regionArea></affiliation></author><author><name sortKey="Evans, Alun" sort="Evans, Alun" uniqKey="Evans A" first="Alun" last="Evans">Alun Evans</name></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus</institution><addr-line>Hinxton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Hinxton</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="au4"><institution>Program in Medical and Population Genetics and Genetic Analysis Platform, Broad Institute of Massachusetts Institute of Technology and Harvard</institution><addr-line>Cambridge, MA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au5"><institution>Department of Medical Genetics, University of Helsinki and University Central Hospital</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au11"><institution>Institute for Molecular Medicine Finland, University of Helsinki</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Markus, Hugh S" sort="Markus, Hugh S" uniqKey="Markus H" first="Hugh S" last="Markus">Hugh S. Markus</name><affiliation wicri:level="1"><nlm:aff id="au6"><institution>Stroke and Dementia Research Centre, St George's University of London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author><author><name sortKey="Grant, Peter J" sort="Grant, Peter J" uniqKey="Grant P" first="Peter J" last="Grant">Peter J. Grant</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Division of Cardiovascular and Diabetes Research, University of Leeds</institution><addr-line>Leeds, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leeds</wicri:regionArea></affiliation></author><author><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D" last="Spector">Tim D. Spector</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Twin Research and Genetic Epidemiology, King's College London</institution><addr-line>London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London</wicri:regionArea></affiliation></author></analytic><series><title level="j">Annals of Neurology</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective</title><p>End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.</p></sec><sec><title>Methods</title><p>Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3).</p></sec><sec><title>Results</title><p>Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (<italic>p</italic> < 5 × 10<sup>–8</sup>) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (<italic>p</italic> = 2.6 × 10<sup>–186</sup>), rs10665 with FVII (<italic>p</italic> = 2.4 × 10<sup>–47</sup>), and rs505922 in the <italic>ABO</italic> gene with both von Willebrand factor (<italic>p</italic> = 4.7 × 10<sup>–57</sup>) and factor VIII (<italic>p</italic> = 1.2 × 10<sup>–36</sup>). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88–0.99, <italic>p</italic> = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), <italic>p</italic> = 0.001, a finding specific to large-vessel and cardioembolic stroke (<italic>p</italic> = 0.001 and <italic>p</italic> = < 0.001, respectively) but not seen with small-vessel stroke (<italic>p</italic> = 0.811).</p></sec><sec><title>Interpretation</title><p><italic>ABO</italic> gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. 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